Infectious Burden and Immortal-Time Bias During AML Induction: A Supportive-Care Cohort Under Posaconazole Prophylaxis
4 affiliations
- 1Department of Hematology, Bursa Yüksek İhtisas Training and Research Hospital, University of Health Sciences, 16310 Bursa, Turkey
- 2Department of Internal Medicine, Antalya Training and Research Hospital, 07100 Antalya, Turkey
- 3Department of Hematology, Faculty of Medicine, Bursa Uludağ University, 16059 Bursa, Turkey
- 4Department of Hematology, Antalya Training and Research Hospital, 07100 Antalya, Turkey
Abstract
Background/Objectives: Infection is a major complication of acute myeloid leukaemia (AML) induction, and analyses relating treatment-emergent infection to survival are prone to immortal-time bias. We characterised baseline and treatment-emergent infection during induction and used bias-aware methods to distinguish a pre-treatment risk signal from a survival-time artefact. Methods: Our study analysed a retrospective single-centre cohort of 91 adults with newly diagnosed AML receiving induction under universal posaconazole prophylaxis (2019–2025) with Cox models, 14- and 30-day landmark analyses and Firth penalised logistic regression. Results: Active infection at diagnosis occurred in 23/91 (25.3%) and treatment-emergent infection in 54/91 (59.3%). A naive Cox model showed an implausibly protective association for treatment-emergent infection (hazard ratio [HR] 0.46, 95% CI 0.21–0.99). In 14- and 30-day landmark analyses (HR 0.59 and 0.60; 95% CIs included 1) the estimate moved toward the null and lost statistical significance; because infection-onset dates were unavailable, landmark analysis only partially corrects this bias, and the independent association between treatment-emergent infection and survival could not be reliably estimated. Active infection at diagnosis showed a fragile, exploratory association with later mortality that was nominally significant in only one of several pre-specified specifications (30-day landmark HR 2.56, 95% CI 1.03–6.37). Conclusions: The apparently protective association of treatment-emergent infection with survival is consistent with immortal-time bias; it is a complication and marker of course, not a survival determinant. Baseline infection is a hypothesis-generating candidate pre-treatment risk marker that requires prospective validation.
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BibTeX
@article{gozden2026infectious,
title = {{Infectious Burden and Immortal-Time Bias During AML Induction: A Supportive-Care Cohort Under Posaconazole Prophylaxis}},
author = {Hilmi Erdem Gözden and Halime Betül Tokat and Hamide Tuğba Uluçay and Fatma Tuğçe Bayrak and Recep Kaya and Alperen Burak Kocabıyık and Süleyman Emre Okutan and İbrahim Ethem Pınar and Erdal Kurtoğlu and Volkan Karakuş},
journal = {Journal of Clinical Medicine},
year = {2026},
month = oct,
doi = {10.3390/jcm15207841},
url = {https://www.mdpi.com/2077-0383/15/20/7841},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Infectious Burden and Immortal-Time Bias During AML Induction: A Supportive-Care Cohort Under Posaconazole Prophylaxis
AU - Hilmi Erdem Gözden
AU - Halime Betül Tokat
AU - Hamide Tuğba Uluçay
AU - Fatma Tuğçe Bayrak
AU - Recep Kaya
AU - Alperen Burak Kocabıyık
AU - Süleyman Emre Okutan
AU - İbrahim Ethem Pınar
AU - Erdal Kurtoğlu
AU - Volkan Karakuş
PY - 2026
DA - 2026/10/01
JO - Journal of Clinical Medicine
DO - 10.3390/jcm15207841
UR - https://www.mdpi.com/2077-0383/15/20/7841
AB - Background/Objectives: Infection is a major complication of acute myeloid leukaemia (AML) induction, and analyses relating treatment-emergent infection to survival are prone to immortal-time bias. We characterised baseline and treatment-emergent infection during induction and used bias-aware methods to distinguish a pre-treatment risk signal from a survival-time artefact. Methods: Our study analysed a retrospective single-centre cohort of 91 adults with newly diagnosed AML receiving induction under universal posaconazole prophylaxis (2019–2025) with Cox models, 14- and 30-day landmark analyses and Firth penalised logistic regression. Results: Active infection at diagnosis occurred in 23/91 (25.3%) and treatment-emergent infection in 54/91 (59.3%). A naive Cox model showed an implausibly protective association for treatment-emergent infection (hazard ratio [HR] 0.46, 95% CI 0.21–0.99). In 14- and 30-day landmark analyses (HR 0.59 and 0.60; 95% CIs included 1) the estimate moved toward the null and lost statistical significance; because infection-onset dates were unavailable, landmark analysis only partially corrects this bias, and the independent association between treatment-emergent infection and survival could not be reliably estimated. Active infection at diagnosis showed a fragile, exploratory association with later mortality that was nominally significant in only one of several pre-specified specifications (30-day landmark HR 2.56, 95% CI 1.03–6.37). Conclusions: The apparently protective association of treatment-emergent infection with survival is consistent with immortal-time bias; it is a complication and marker of course, not a survival determinant. Baseline infection is a hypothesis-generating candidate pre-treatment risk marker that requires prospective validation.
SN - 2077-0383
ER -